Sulfonamide compounds

ABSTRACT

THE PRESENT INVENTION IS DIRECTED TO NOVEL COMPOUNDS OF THE FORMULA   (3,5-DI(O2N-),4-(R1-N(-R2)-)PHENYL)-SO2-N(-R3)-CH2-N(-R4)2   WHICH COMPOUNDS ARE USEFUL AS HERBICIDES. IN THE ABOVE AND SUCCEEDING FORMULAE HEREIN, R1 REPRESENTS HYDROGEN OR R2, AND EACH R2 INDEPENDENTLY REPRESENTS LOWERALKYL OF C1-C6 LOWERALKENYL OF C2-C6 LOWERALKYNYL OF C2-C6, OR RADICAL OF THE FORMULA-CH2-CH2-CH2$2Y WHEREIN A REPRESENTS 0 OR 1, AND Y REPRESENTS METHOXY, CYANO, BROMO, OR CHLORO, SUBJECT TO THE LIMITATION THAT THE GROUPS REPRESENTED BY R1 AND R2 TOGETHER CONTAIN FROM 2 TO 8, BOTH INCLUSIVE, CARBON ATOMS; R1 REPRESENTS HYDROGEN OR METHYL; AND EACH R4, IF TAKEN SEPARATELY, REPRESENTS PROPYL, OR BOTH R4, IF TAKEN TOGETHER, JOINTLY CONSTITUTE WITH THE NITROGEN ATOM AN AZIRIDINE, PYRROLIDINE, PIPERIDINE, HEXAHYDROAZEPINE, MORPHOLINE, O PIPERAZINE RING, OR SUCH RING BEARING MONO-OR DILOWERALKYL SUBSTITUTION OF A TOTAL OF NOT MORE THAN 3 CARBON ATOMS.

United States Patent 3,772,277 SULFONAMIDE COMPOUNDS James R. Beck,Indianapolis, Ind., assignor to Eli Lilly and Company, Indianapolis,Ind. No Drawing. Filed June 28, 1971, Ser. No. 157,679 Int. Cl. C07c143/00 US. Cl. 260-2396 6 Claims ABSTRACT OF THE DISCLOSURE The presentinvention is directed to novel compounds of the formula N- SO2NCH2-N R1I \R4 NO: which compounds are useful as herbicides. In the above andsucceeding formulae herein, R represents hydrogen or R and each Rindependently represents loweralkyl of C -C loweralkenyl of C -Cloweralkynyl of C -C or radical of the formula CH CH CH Y wherein nrepresents 0 or 1, and Y represents methoxy, cyano, 'bromo, or chloro,subject to the limitation that the groups represented by R and Rtogether contain from 2 to 8, both inclusive, carbon atoms; R representshydrogen or methyl; and each R if taken separately, represents propyl,or both R if taken together, jointly constitute with the nitrogen atoman aziridine, pyrrolidine, piperidine, hexahydroazepine, morpholine, orpiperazine ring, or such ring bearing monoor diloweral-kyl substitutionof a total of not more than 3 carbon atoms.

DETAILED DESCRIPTION OF THE INVENTION The present invention is directedto compounds of the formula wherein R R R and R are as definedhereinabove. The compounds are typically crystalline solids. They areprepared by the Mannich reaction, using formaldehyde, a sulfanilamidecompound of the formula N02 R l N- -S02NH R R N02 and an amine of theformula RI EN The reaction is conducted in accordance with standardprocedures for the Mannich reaction; see, e.g., Blicke, OrganicReactions (John Wiley & Sons, Inc., New York, N.Y., 1942), vol. 1, p.303 et seq.; and Hellman and Teichmann, Berichte, vol. 91, p. 2432 etseq. In general, the sulfanilamide is mixed with the amine, and theformaldehyde added as an aqueous solution or a paraformaldehyde. Asolvent, such as an alcohol, can be used but is generallyunnecessarywhen the formaldehyde is supplied as a liquid. The reactiongoes forward over a wide range of temperatures, for example, from roomtemperature to reflux temperatures. Separation, and if desired,purification, are carried out in conventional procedures.

The compounds of the present invention are named herein as substitutedsulfanilamides, with structure and position identification as follows:

Patented Nov. 13, 1973 "ice Aliphatic groups are straight-chain unlessotherwise identified.

The following examples illustrate the present invention and will enablethose skilled in the art to synthesize all of the compounds of thepresent invention.

EXAMPLE 1 N -piperidinomethyl-3,5-dinitro-N ,N dipropylsulfanilamide3,5-dinitro-N ,N -dipropylsulfanilamide (4.0 grams; 0.012 mole) andformaldehyde (1.0 milliliter) were dissolved in ethanol and piperidine(0.8 gram; 0.011 mole) added. The addition caused a temperature rise andprecipitation of a yellow product, the desired N-piperidinomethyl-3,5-dinitro-N ,N -dipropylsulfanilamide. It wasseparated by filtration, washed with water, and recrystallized fromethanol, M.P., 138-40 C.

Analysis.-Calc. (percent): C, 48.75; H, 6.59; N, 15.79. Found (percent):C, 48.04; H, 6.22; N, 15.68.

EXAMPLES 2-12 Other representative compounds of the present invention,prepared in accordance with the foregoing teachings and examples, arethe following:

EXAMPLES 13-22 Yet other representative compounds illustrative of thepresent invention are the following:

N -(3-methylpiperidinomethyl)-3,5-dinitro-N ,N -dir methylsulfanilamide.N -methyl-N -aziridinomethyl-3,5-dinitro-N -methyl- N-butylsulfanilamide. N -piperidinomethyl-3,5-dinitro-N ,N-bis(Z-methoxyethyl)-sulfanilamide. N -morpho1inomethyl-3,5-dinitro-N-isopropylsulfanilamide. N -hexahydroazepinomethyl-3,5-dinitro-N ,N-diallylsulfanilamide. N -pyrrolidinomethyl-3,5-dinitro-N ,N-bis(Z-cyanoethyl)-sulfanilamide. N l-piperazinylmethyl) -3,5-dinitro-N,N -dipropynylsulfanilamide.

3 N -aziridinomethyl-3,5 -dinitro-N ,N -bis 2-chloroethyl)sulfanilamide. N l-piperazinylmethyl) -3,5-dinitro-N ,N -bis(3-bromopropyl) -sulfanilamide. N -pyrrolidinomethyl-3,5-dinitro-N ,N-dibutylsulfanilamide.

The compounds of the present invention are adapted to be employed asherbicides. The compounds can be utilized to achieve broad herbicidalaction; hence, in its broadest sense, the present invention is directedto a method which comprises applying to a plant part, which can be astem, leaf, flower, fruit, root, or seed or other similar reproductiveunit of a plant, a growth-inhibiting amount of one of the compounds ofthe present invention. However, the compounds can also be utilized totake advantage of selective patterns of herbicidal activity.

It is not critical to the practice of the present invention thatcomplete destruction of undesirable vegetation be obtained, it beingadequate if the growth of the unwanted vegetation is merely inhibited.Especially where selective action is sought, inhibition falling short ofactual killing is adequate, particularly when combined with naturallyoccurring conditions such as limited moisture and the like which moreadversely affect the vegetation selectively inhibited than the cropplant.

The compounds of the present invention are suited to a wide variety ofherbicidal applications. Thus, for example, at rates which evoke theselective action of the compounds, which rates are defined morecompletely hereinbelow, the compounds can be used as selectiveherbicides in crop plants, such as, for example, cotton, corn, sorghum,soybeans, and the like. In such use, application can be made preemergentto both crops and weeds, or, preferably by means of a directed sprayapplication technique, postemergent to the crop plant but bothpreemergent and postemergent to the weeds. In another application, thecompounds can be used to give broad herbicidal action on non-crop land,including intermittently non-crop strips of contour-farmed land. Forsuch usage on so-called fallow land, application can be made in springto suppress vegetative growth until a fall or following spring planting,or in the fall to suppress vegetative growth until a spring or followingfall planting. Furthermore, in another application, the presentcompounds can be utilized to control weeds in tree crop plantings, suchas plantings of the various citrus trees. Also, the compounds can beused for turf applications. In addition to the foregoing terrestrialembodiments, the present compounds can also be utilized as aquaticherbicides.

The practice of the present invention in any of its numerous embodimentscan in some instances be carried out with unmodified compound; however,for good results, it is generally necessary that the compound beemployed in modified form, that is, as one component of a compositionformulated to implement the plant growth-inhibiting effects. Thus, forexample, the active agent can be mixed with water or other liquid orliquids, preferably aided by the usage of a surface active agent. Theactive agent can also be incorporated on a finely divided solid, whichcan be a surface active substance, to yield a wettable powder, which cansubsequently be dispersed in water or other liquid, or incorporated aspart of a dust which can be applied directly. Other methods offormulations are known in the art and can be employed in implementingthe present invention.

In carrying out the novel method of the present invention, the exactamount of the active agent employed is not critical and will vary,depending upon the type of growthinhibiting effect desired, the identityof the plants concerned, the particular active agent used, weatherconditions, and the like. In general, a broad growth-inhibiting effectis obtained with rates of from about 8 to pounds or more of active agentper acre, and such rates are suitable and effective for control ofvegetative growth on fallow land. When it is desired to obtain aselective growth-inhibiting effect on weeds in areas containing cropplants such as corn, soybeans, and cotton, rates of from 0.25 to about 8pounds generally give good results. When in the typical mode ofoperation, the active agent is employed as a composition comprising theagent, the exact concentration of active agent in the composition is notcritical, except that the concentration and total amount of formulationemployed be adequate to supply the appropriate amount of active agent ona per acre basis. In general, good results are obtained when employingformulations containing the active agent in a concentration of from 0.5to 10 percent or higher, in the instance of a liquid formulation; and ina concentration of from 1.0 to 5.0 percent or higher, in the instance ofa dust, powder, granule, or the like. More concentrated formulations canbe prepared and are often preferred in that they can serve, dependingupon the particular application contemplated and the articularconcentration, both as a concentrated formulation for purposes ofshipment, storage, and the like, and as an ultimate treatingcomposition. Thus, for example, formulations often preferably contain asurface active agent and the present active agent, the latter beingpresent in an amount of from 0.5 to 99.5 percent, by weight; or aninert, finely divided solid and the present active agent, the latterbeing present in an amount of from 1.0 to 99.0 percent, by weight. Suchformulations, as indicated, can be employed directly, in certainapplications, but can also be diluted and subsequently employed in manyother applications.

Liquid compositions containing the desired amount of active agent areprepared by dissolving the substance in a liquid, with or without theaid of a surface active dispersing agent such as an ionic or non-ionicemulsifying agent. Suitable liquids include agricultural spray oils andthe petroleum distillates such as diesel fuel, kerosene, fuel oilnaphthas and Stoddard solvent. The choice of dispersing and emulsifyingagent and the amount thereof employed is dictated by the nature of thecomposition and by the ability of the agent to facilitate the dispersionof the active agent in the carrier to produce the desired composition.Dispersing and emulsifying agents which can be employed in thecompositions include the condensation products of alkylene oxides withphenols and organic acids, alkyl aryl sulfonates, polyoxyalkylenederivatives or sorbitan esters, complex ether alcohols, and the like.Representative surface active agents which are suitably employed inimplementing the present invention are identified in U.S. Pats.3,095,299, second column, lines 25-36, 2,655,447, column 5, and2,412,510, columns 4 and 5.

In the preparation of dust compositions, the active ingredient isintimately dispersed in and on a finely divided solid such as clay,talc, chalk, gypsum, limestone vermiculite fines, perlite, and the like.In one method of achieving such dispersion, the finely divided carrieris mechanically mixed or ground with the active agent.

Similarly, dust compositions containing the toxicant compounds can beprepared with various of the solid surface active dispersing agents suchas bentonite, fullers earth, attapulgite and other clays. Depending uponthe proportions of ingredients, these dust compositions can be employedas concentrates and subsequently diluted with additional solid surfaceactive dispersing agents or with chalk, talc, or gypsum and the like toobtain the desired amount of active ingredient in a composition adaptedto be employed for the suppression of the growth of the plants. Also,such dust compositions can be dispersed in water, with or without theaid of a dispersing agent, to form spray mixtures.

Formulations containing the present active agent are oftenadvantageously further modified by incorporation therein of an effectiveamount of a surfactant which facilitates the dispersion and spreading ofthe formulation on the plant leaf surfaces and the incorporation of theformulation by the plant.

In accordance with the present invention, the active agent can bedispersed in soil or other growth media in any convenient fashion.Applications can be carried out by simply mixing with the media, byapplying to the surface of soil and thereafter dragging or discing intothe soil to the desired depth, or by employing a liquid carrier toaccomplish the penetration and impregnation. The application of sprayand dust compositions to the surface of soil, or to plant parts or theabove ground surfaces of plants can be carried out by conventionalmethods, e.g., power dusters, boom and hand sprayers and spray dusters,whether surface or air-borne.

In a further method, the distribution of the active agent in soil can beaccomplished by introducing the agent into the water employed toirrigate the soil. In such procedures, the amount of water is variedwith the porosity and water holding capacity of the soil to obtain adesired depth of distribution of the agent.

In addition, the present method also comprehends the employment of anaerosol composition containing one or more of the present active agentsas an active compound. Such a composition is prepared according toconventional methods wherein the agent is dispersed in a solvent, andthe resultant dispersion mixed with a propellant in liquid state. Suchvariables as the particular agent to be used and the nature of thevegetation which is to be treated will determine the desirability of thesolvent and concentration of the agent therein.

EXAMPLE 23 The formulation of the compounds of the present invention forthe purpose of conducting the herbicidal evaluation, the results ofwhich are reported hereinbelow, was carried out in accordance withconventional procedures. The compound to be evaluated was initiallysuspended in a 1:1 acetone/ethanol solution of a blend of nonionicsulfonate emulsifying agents. The suspension was then diluted with anaqueous solution of the same blend of agents to obtain the ultimatetreating composition; this composition contained 4.15 percent of each ofthe acetone and ethanol, 1000 p.p.m. of the blend of emulsifying agents,and the respective compounds in an amount to supply the desired poundsper acre. In the instance of some of the lower rates, a formulation soobtained was further diluted with water containing 1000 p.p.m. of theblend of emulsifying agents, only thus further lessening theconcentration of the ethanol and acetone.

6 EXAMPLES 24-35 Various of the compounds of the present invention wereevaluated for preemergent application to various species of plants. Inthis evaluation, a soil was prepared consisting of one part masonry sandand one part shredded top soil blended together in a cement mixer. Onegallon of this soil was placed in a 21.5 x 31.5 cm. galvanized fiat andwas patted down with a bench brush until level. A three-row marker wasused to make 2% cm. deep furrows in approximately two-fifths of thefiat. Crop seeds consisting of four kernels of corn, five cotton seedsand five soybean seeds were placed in these furrows. A four-row templatewas then placed on the remaining soil and the indicated approximatenumbers of each of the following seeds were planted, one species to eachsection: foxtail (millet), 100 seeds; velvetleaf (40-50 seeds); roughpigweed (150-250 seeds); and large crabgrass (-150 seeds).

Suflicient soil was added to cover the entire fiat. Thus, the weed seedswere covered to a depth of about 6 mm. and the crop seeds were coveredto a depth of about 3 cm.

In assaying the effect of the composition as preemergent herbicides, aflat prepared as above, taken either on the day of planting or on thenext day, was placed in a chamber equipped with a turntable and an airexhaust. A herbicidal composition containing the subject compound andprepared as described in the preceding example was applied to the flatwith a modified De Vilbiss atomizer hooked to an air source. Twelve andone-half milliliters of the composition under test wereapplied to eachflat either on the day of planting or the succeeding day. Injury ratingsand observations as to type of injury were made eleven to twelve daysafter treatment. The injury rating scale used was as follows:

0-no injury 1slight injury 2-moderate injury 3-severe injury 4-deathWhen more than one determination was carried out at a given rate, anaverage value was calculated for the injury rating.

In the following table setting forth the results of the evaluation,column 1 gives the name of the compound under test; column 2, the ratein pounds per acre at which the compound was applied to the test fiat;and the remaining columns, the injury to the particular plant seeds orseedlings as measured by the foregoing scale.

TABLE I.INJ'URY RATING ON PREEMERGENT TREATMENT Lbs./ Soy- Crab- Pig-Compound acre Corn Cotton bean grass weed N-dipropylaminomethyl-3,5-dinitro-N ,N -dipropy1su.lianilamide N-(2-ethylpipe1idinomethyl) -3,5-dinitro-N ,N -dipropylsulfauilamide N-hexahydroazepinomethyl-B,5-diuitro-N ,N -dipropylsulfani1amide N-(2,2-dimethylaziridinomethyl)-3,5-dinitro-N ,N -dipropy1sulfanllan1ideN -(3-methylpiperldinomethyl)-3,5-dinitro-N ,N -dlpropylsuli'anilamide N-piperidinomethyl-Ia,5-dinitro-N ,N -dipropylsu1ianilamlde N -methyl-N-piperid1nomethyl-3,5-dinitro-N -N -dipropylsulanilamide.

N -morpholinomethy1-3,5-dlnitro-N ,N dipropylsulianllamide N-(tmethyl-l-piperazinylmethyl)-3,5-dinltro-N ,N -dipropylsulianilamide N-(2,5-dimethy1pyrrolidinomethyl)-3,5-dlnitro-N ,N-dipropylsulfanllamlde.

P zevoewicwcc eomimempeeuuolwwuhthmwwwcnwmewwu caeepww N TABLEICon-tinued Lbs./ Soy- Crab- Pigelvet- Compound acre Corn Cotton beangrass weed Foxtail leaf 8 1 0 4 8 N -methyl-N-morpholinomethywfi-dlnitro-N ,N -dipropylsulfanilamide 4 0 0 1 g 2 2 00 1 2 I V 8 0 3 3 N -(4-methylpiperldinomethyl)-3,5dinitro-N ,N-dipropylsulfanilamide 4 2 1 2 3 4 2 0. 5 0 0 3. 5 2. 5

EXAMPLES 36-45 Essentially the same results as those reported inforegoing Examples 24-35 are obtained when evaluating the followingother representative compounds of the present invention.

N 3-methylpiperidinomethyl) -3,5-dinitro-N ,N

dimethylsulfanilamide.

N -methyl-N -aziridinomethyl-3,5-dinitro-N -methyl-Nfbutylsulfanilamide.

N -piperidinomethyl-3 ,5 -dinitro-N ,N -bis Z-methoxyethyl)sulfanilamide.

N -morpholinomethyl-3 ,5 -dinitro-N -isopropylsulfanilamide.

N -hexahydroazepinomethyl-3, 5 -dinitro-N ,N -diallylsulfanilamide.

N -pyrrolidinomethyl-3,5-dinitro-N ,N -bis (2-cyanoethyl -sulfanilamide.

N l-piperazinylmethyl -3,S-dinitro-N ,N -dipropynylsulfanilamide.

N -aziridinomethyl-3,5-dinitro-N ,N -bis (2-chloroethyl) sulfanilamide.

N l-piperazinylmethyl) -3,5-dinitro-N ,N -bis( 3-bromopropyl)sulfanilamide.

N -pyrrolidinomethyl-3 ,5 -dinitro-N ,N -dibutylsulfanilamide.

Satisfactory results are obtained when the active agent of the presentinvention, or a composition comprising such active agent, is combinedwith other agricultural materials intended to be applied to plants,plant parts, or their habitats. Such materials include fertilizers,fungicides, nematocides, insecticides, other herbicides, soilconditioning agents, and the like.

I claim: 1. The compound of the formula N 01 R1 R4 N S Oz-II-GHz-N R1'13 3,;

N O z wherein R represents hydrogen or R and each R independentlyrepresents loweralkyl of C -C loweralkenyl of C -C loweralkynyl of C -Cor radical of the formula CH CH (-CH Y wherein n represents 0 or 1, andY represents methoxy, cyano, bromo, or chloro, subject to the limitationthat the groups represented by R and R together contain from 2 to 8,both inclusive, carbon atoms; R represents hydrogen or methyl; and eachR if taken separately, represents propyl, or both R if taken together,jointly constitute with the nitrogen atom an aziridine, pyrrolidine,piperidine, hexahydroazepine, morpholine, or piperazine ring, or suchring bearing monoor diloweralkyl substitution of a total of not morethan 3 carbon atoms.

2. The compound of claim 1 which is N -piperidinomethyl-3,5-dinitro-N ,N-dipropylsulfanilamide.

3. The compound of claim 1 which is N -(2,5-dimethylpyrrolidinomethyl)3,5 dinitro N ,N dipropylsul fanilamide.

4. The compound of claim 1 which is N -methyl-Npiperidinomethyl-3,5-dinitro-N ,N -dipropylsulfanilamide.

5. The compound of claim 1 which is N -(2-ethylpiperidinomethyl) 3,5dinitro N ,N dipropylsul fanilamide.

6. The compound of claim 1 which is N-hexahydroazepinomethyl-3,S-dinitro-N ,N -dipropylsulfanilamide.

References Cited UNITED STATES PATENTS 2,834,793 5/1958 Livingston eta1. 260-397.7 3,367,949 2/1968 Soper 260239.6 3,382,260 5/1968 Gruenmanet a1. 260397.7

HENRY R. JILES, Primary Examiner R. T. BOND, Assistant Examiner U.S. Cl.X.R.

